The experiments of this proposal would analyze the plastic modifications of central neuronal circuitry which occur in response to brain lesions in adult rats. Both the structural alterations, and the functional consequences of afferent re-organization would be analyzed. Previous studies have shown that unilateral destruction of the entorhinal cortex of the rat induces a proliferative response in the afferents from the contralateral entorhinal cortex, which sprout and grow to reinnervate some of the neurons which had lost their normal input as a consequence of the lesion. This process of post-lesion fiber growth and synaptogenesis is analyzed in this model system, determining (1) which entorhinal cortical neurons sprout; (2) how the new sprouts compare anatomically with the normal projections which are replaced; (3) where the new sprouts depart from the parent axons and how they travel into the denervated regions; (4) what the selective controls are which determine whether a given afferent will or will not reinnervate a denervated region; and, (5) how the new pathway constructed in response to the lesion compares physiologically with the normal pathway which had been destroyed.